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In JoVE (1)
Other Publications (11)
- Academic Medicine : Journal of the Association of American Medical Colleges
- Biochemical and Biophysical Research Communications
- Journal of Neurochemistry
- Stroke; a Journal of Cerebral Circulation
- Anesthesia and Analgesia
- Biochimica Et Biophysica Acta
- Journal of Immunology (Baltimore, Md. : 1950)
- Current Opinion in Neurology
- Stroke; a Journal of Cerebral Circulation
- Stroke; a Journal of Cerebral Circulation
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Articles by Vincent Prinz in JoVE
السكتة الدماغية النمذجة في الفئران -- الشرق انسداد الشريان الدماغي مع نموذج الشعيرة
Odilo Engel, Sabine Kolodziej, Ulrich Dirnagl, Vincent Prinz
Department for Experimental Neurology, Center for Stroke Research Berlin, Charité Universitätsmedizin
الخيطية انسداد الشريان الدماغي الأوسط هو نموذج مشترك لدراسة السكتة الدماغية لدى الفئران.
Other articles by Vincent Prinz on PubMed
A Medical Humanities Special Study Module on Principles of Medical Theory and Practice at the Charité, Humboldt University, Berlin, Germany
Academic Medicine : Journal of the Association of American Medical Colleges. Oct, 2003 | Pubmed ID: 14534104
The authors are members of a committee in charge of a special study module (SSM) entitled Principles of Medical Theory and Practice in a problem-based and integrated reformed curriculum track at the Charité, the medical school and university hospital of the Humboldt University, Berlin, Germany. The SSM contextualizes medicine by highlighting the societal contexts of the doctor-patient relationship and the medical profession. Integrating the humanities into medical education helps students develop an awareness of the strengths and limitations of modern medicine, develop their own personalities and sense of social responsibility, and generally broaden their outlook. Teachers in the SSM seminars are from different disciplines, such as the history of medicine, bioethics, sociology, anthropology, and complementary medicine. Once a week, one or two teachers meet with as many as 21 students per group for a 90-minute course. Twelve courses constitute a seminar. Students are required to participate in four seminars during five years of studies. They can choose different topics from a set range. Although this SSM has been largely successful, some problems have occurred. Results from the course evaluations and experiences show that the seminars differ from one another in many ways. Financial restraints and the departmental structure of the faculty have influenced implementation of the SSM. However, the SSM is a new concept and is continuously reviewed and renewed. Future plans will be to specify outcomes, continue to discuss reasonable seminar topics, establish continuous support and training for teachers, and motivate students to become actively involved in the seminar discussions.
Biochemical and Biophysical Research Communications. Aug, 2007 | Pubmed ID: 17548055
A significant up-regulation of Toll-like-receptor (TLR) mRNAs between 3 and 48 h reperfusion time after induction of transient focal cerebral ischemia for 1h was revealed by applying global gene expression profiling in postischemic mouse brains. Compared to TLR4 and TLR9, TLR2 proved to be the most significantly up-regulated TLR in the ipsilateral brain hemisphere. TLR2-protein was found to be expressed mainly in microglia in the postischemic brain tissue, but also in selected endothelial cells, neurons, and astrocytes. Additionally, TLR2-related genes with pro-inflammatory and pro-apoptotic capabilities were induced. Therefore we hypothesized that TLR2-signaling could exacerbate the primary brain damage after ischemia. Two days after induction of transient focal cerebral ischemia (1h), we found a significant decrease of the infarct volume in TLR2 deficient mice compared to wild type mice (75+/-5 vs. 42+/-7 mm(3)). We conclude that TLR2 up-regulation and TLR2-signaling are important events in focal cerebral ischemia and contribute to the deterioration of ischemic damage.
Pituitary Adenylate Cyclase-activating Polypeptide is Up-regulated in Cortical Pyramidal Cells After Focal Ischemia and Protects Neurons from Mild Hypoxic/ischemic Damage
Journal of Neurochemistry. Nov, 2007 | Pubmed ID: 17868305
The protective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) in stroke models is poorly understood. We studied patterns of PACAP, vasoactive intestinal peptide, and the PACAP-selective receptor PAC1 after middle cerebral artery occlusion and neuroprotection by PACAP in cortical cultures exposed to oxygen/glucose deprivation (OGD). Within hours, focal ischemia caused a massive, NMDA receptor (NMDAR)-dependent up-regulation of PACAP in cortical pyramidal cells. PACAP expression dropped below the control level after 2 days and was normalized after 4 days. Vasoactive intestinal peptide expression was regulated oppositely to that of PACAP. PAC1 mRNA showed ubiquitous expression in neurons and astrocytes with minor changes after ischemia. In cultured cortical neurons PACAP27 strongly activated Erk1/2 at low and p38 MAP kinase at higher nanomolar concentrations via PAC1. In astrocyte cultures, effects of PACAP27 on Erk1/2 and p38 were weak. During OGD, neurons showed severely reduced Erk1/2 activity and dephosphorylation of Erk1/2-regulated Ser112 of pro-apoptotic Bad. PACAP27 stimulation counteracted Erk1/2 inactivation and Bad dephosphorylation during short-term OGD but was ineffective after expanded OGD. Consistently, PACAP27 caused MEK-dependent neuroprotection during mild but not severe hypoxic/ischemic stress. While PACAP27 protected neurons at 1-5 nmol/L, full PAC1 activation by 100 nmol/L PACAP exaggerated hypoxic/ischemic damage. PACAP27 stimulation of astrocytes increased the production of Akt-activating factors and conferred ischemic tolerance to neurons. Thus, ischemia-induced PACAP may act via neuronal and astroglial PAC1. PACAP confers protection to ischemic neurons by maintaining Erk1/2 signaling via neuronal PAC1 and by increasing neuroprotective factor production via astroglial PAC1.
Glia. Feb, 2008 | Pubmed ID: 18098126
Microglia is activated by brain injury. They migrate in response to ATP and although adenosine alone has no effect on wild type microglial migration, we show that inhibition of adenosine receptors impedes ATP triggered migration. CD39 is the dominant cellular ectonucleotidase that degrades nucleotides to nucleosides, including adenosine. Importantly, ATP fails to stimulate P2 receptor mediated migration in cd39(-/-) microglia. However, the effects of ATP on migration in cd39(-/-) microglia can be restored by co-stimulation with adenosine or by addition of a soluble ectonucleotidase. We also tested the impact of cd39-deletion in a model of ischemia, in an entorhinal cortex lesion and in the facial nucleus after facial nerve lesion. The accumulation of microglia at the pathological sites was markedly decreased in cd39(-/-) animals. We conclude that the co-stimulation of purinergic and adenosine receptors is a requirement for microglial migration and that the expression of cd39 controls the ATP/adenosine balance.
Stroke; a Journal of Cerebral Circulation. Feb, 2008 | Pubmed ID: 18162625
Statins exert rapid cholesterol-independent vasoprotective effects. Here, we tested whether postevent treatment with intravenously (i.v.) administered rosuvastatin improves acute stroke outcome in mice.
Anesthesia and Analgesia. Aug, 2009 | Pubmed ID: 19608834
The introduction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, i.e., statins, constitutes a milestone in the prevention of cardio- and cerebrovascular disease. The effects of statins extend far beyond their effects on cholesterol levels: pleiotropic effects include vasoprotective mechanisms, comprising improved endothelial function, increased bioavailability of nitric oxide, immunomodulatory and antiinflammatory properties, stabilization of atherosclerotic plaques, as well as antioxidant and stem cell-regulating capacities. Large clinical trials have clearly demonstrated that statins reduce the risk of myocardial infarction and stroke. Recent experimental and clinical data have demonstrated that in addition to risk reduction, statins may also improve outcome after stroke and myocardial infarction, even when statins were administered after the event. Moreover, abrupt discontinuation of statin therapy after acute cardio- or cerebrovascular events may impair vascular function and increase morbidity and mortality. Beyond stroke, statin treatment also has been shown to provide protective effects in critically ill patients, e.g., after major surgery, sepsis, or in patients at high-vascular risk. However, although large randomized controlled trials are missing, ongoing trials will clarify the impact of acute statin treatment in these conditions. Although evidence is presently limited, acute statin therapy is emerging as a new therapeutic avenue for the treatment of the critically ill. Until now, statins were only available as oral drugs. An IV formulation may be warranted for acute treatment of severely ill patients, for example, those who are unable to swallow or scheduled for surgery. Hydrophilic statins would be suitable for an IV formulation and have been safely tested in healthy volunteers.
Biochimica Et Biophysica Acta. Dec, 2009 | Pubmed ID: 19835955
Several reports have recently demonstrated a detrimental role of Toll-like receptors (TLR) in cerebral ischemia, while there is little information about the endogenous ligands which activate TLR-signaling. The myeloid related proteins-8 and-14 (Mrp8/S100A8; Mrp14/S100A9) have recently been characterized as endogenous TLR4-agonists, and thus may mediate TLR-activation in cerebral ischemia. Interestingly, not only TLR-mRNAs, but also Mrp8 and Mrp14 mRNA were found to be induced in mouse brain between 3 and 48 h after transient 1 h focal cerebral ischemia/reperfusion. Mrp-protein was expressed in the ischemic hemisphere, and co-labeled with CD11b-positive cells. To test the hypothesis that Mrp-signaling contributes to the postischemic brain damage, we subjected Mrp14-deficient mice, which also lack Mrp8 protein expression, to focal cerebral ischemia. Mrp14-deficient mice had significantly smaller lesion volumes when compared to wild-type littermates (130+/-16 mm(3) vs. 105+/-28 mm(3)) at 2 days after transient focal cerebral ischemia (1 h), less brain swelling, and a reduced macrophage/microglia cell count in the ischemic hemisphere. We conclude that upregulation and signaling of Mrp-8 and-14 contribute to neuroinflammation and the progression of ischemic damage.
Journal of Immunology (Baltimore, Md. : 1950). Jun, 2010 | Pubmed ID: 20439917
The stem-cell marker CD93 (AA4.1/C1qRp) has been described as a potential complement C1q-receptor. Its exact molecular function, however, remains unknown. By using global expression profiling we showed that CD93-mRNA is highly induced after transient focal cerebral ischemia. CD93 protein is upregulated in endothelial cells, but also in selected macrophages and microglia. To elucidate the potential functional role of CD93 in postischemic brain damage, we used mice with a targeted deletion of the CD93 gene. After 30 min of occlusion of the middle cerebral artery and 3 d of reperfusion these mice displayed increased leukocyte infiltration into the brain, increased edema, and significantly larger infarct volumes (60.8 +/- 52.2 versus 23.9 +/- 16.6 mm(3)) when compared with wild-type (WT) mice. When the MCA was occluded for 60 min, after 2 d of reperfusion the CD93 knockout mice still showed more leukocytes in the brain, but the infarct volumes were not different from those seen in WT animals. To further explore CD93-dependent signaling pathways, we determined global transcription profiles and compared CD93-deficient and WT mice at various time points after induction of focal cerebral ischemia. We found a highly significant upregulation of the chemokine CCL21/Exodus-2 in untreated and treated CD93-deficient mice at all time points. Induction of CCL21 mRNA and protein was confirmed by PCR and immunohistochemistry. CCL21, which was formerly shown to be released by damaged neurons and to activate microglia, contributes to neurodegeneration. Thus, we speculate that CD93-neuroprotection is mediated via suppression of the neuroinflammatory response through downregulation of CCL21.
Current Opinion in Neurology. Feb, 2011 | Pubmed ID: 21150596
Large clinical trials have clearly demonstrated that statins reduce the risk of first and recurrent stroke. This review aims to highlight the current findings and recent developments in this field.
Heart Rate Contributes to the Vascular Effects of Chronic Mental Stress: Effects on Endothelial Function and Ischemic Brain Injury in Mice
Stroke; a Journal of Cerebral Circulation. Jun, 2011 | Pubmed ID: 21527760
Vascular effects of mental stress are only partially understood. Therefore, we studied effects of chronic stress and heart rate (HR) on endothelial function and cerebral ischemia.
Stroke; a Journal of Cerebral Circulation. Nov, 2011 | Pubmed ID: 21921276
Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.